Long noncoding RNA LINC00339 promotes renal tubular epithelial pyroptosis by regulating the miR‐22‐3p/NLRP3 axis in calcium oxalate–induced kidney stone

Article

作者: Xu, Hanjiang ; Hao, Zongyao ; Gong, Binbin ; Song, Zhengyao ; Zhang, Yangyang ; Liang, Chaozhao

Abstract:

This study aims to investigate the role of long noncoding RNA (lncRNA) long intergenic nonprotein coding RNA 339 (LINC00339) in regulating renal tubular epithelial pyroptosis in kidney stones and to explore the underlying mechanism. The human renal proximal tubular epithelial (HK‐2) cells were treated with calcium oxalate monohydrate (COM) for 72 hours to establish the cell model of renal tubular injury. Relative expression of LINC00339 and miR‐22‐3p was measured by real‐time quantitative reverse transcription polymerase chain reaction. Expression of pyroptosis‐related molecules was measured by Western blot analysis (NLRP3, ASC, and cleaved caspase‐1 p10) and enzyme‐linked immunosorbent assay (interleukin‐1β [IL‐1β] and IL‐18). Pyroptosis was also determined by lactate dehydrogenase release and active caspase‐1‐propidium iodide double staining. Luciferase reporter assays were performed to verify whether miR‐22‐3p could bind to LINC00339 or NLRP3. We observed increased LINC00339, decreased miR‐22‐3p, NLRP3 inflammasome activation, and enhanced cell pyroptosis in COM‐treated HK‐2 cells. Furthermore, overexpression of both LINC00339 and NLRP3 activated NLRP3 inflammasome and promoted pyroptosis in COM‐treated HK‐2 cells, whereas miR‐22‐3p mimic and NLRP3 knockdown exerted the opposite effects. Mechanically, LINC00339 functioned as a competitive endogenous RNA by sponging miR‐22‐3p to facilitate NLRP3 expression. In conclusion, lncRNA LINC00339 promotes cell pyroptosis by sponging miR‐22‐3p to regulate NLRP3 expression in COM‐treated HK‐2 cells.

2016-03-01·Biochemical pharmacology2区 · 医学

Intestinal anti-inflammatory activity of calcium pyruvate in the TNBS model of rat colitis: Comparison with ethyl pyruvate

2区 · 医学

Article

作者: Camuesco, D ; Rodriguez-Cabezas, M E ; Vezza, T ; Algieri, F ; Utrilla, P ; Galvez, J ; Garrido-Mesa, J ; Garrido-Mesa, N ; Pischel, I ; Rodriguez-Nogales, A

Pyruvate is a key intermediate of the carbohydrate metabolism with endogenous scavenger properties. However, it cannot be used in clinics due to its instability. Ethyl pyruvate (EP) has shown better stability as well as an antioxidant and anti-inflammatory activity. Calcium pyruvate monohydrate (CPM) is another stable pyruvate derivative that could also provide the benefits from calcium, fundamental for bone health. Considering everything, we propose CPM as a therapeutic strategy to treat diseases with an immune component in which there is also a significant dysregulation of the skeletal homeostasis. This could be applicable to inflammatory bowel disease, which is characterized by over-production of pro-inflammatory mediators, including cytokines and reactive oxygen and nitrogen metabolites that induces intestinal mucosal damage and chronic inflammation, and extra-intestinal symptoms like osteopenia and osteoporosis. The effects of CPM and EP (20, 40 and 100mg/kg) were evaluated on the trinitrobenzenesulfonic acid (TNBS) model of colitis in rats, after a 7-day oral treatment, with main focus on colonic histology and inflammatory mediators. Both pyruvates showed intestinal anti-inflammatory effects in the TNBS-induced colitis. They were evident both histologically, with a recovery of the mucosal cytoarchitecture and a reduction of the neutrophil infiltration, and through the profile of inflammatory mediators (IL-1, IL-6, IL-17, IL-23, iNOS). However, CPM appeared to be more effective than ethyl pyruvate. In conclusion, CPM exerts intestinal anti-inflammatory effect on the TNBS-induced colitis in rats, although further experiments are needed to explore its beneficial effects on bone health and osteoporosis.

2016-01-01·American journal of translational research

Role of nanobacteria in the pathogenesis of kidney stone formation.

Article

作者: Hong, Xin ; Wang, Tian ; Wang, Xiaofeng ; Li, Hui ; Yu, Chengfan

OBJECTIVE:

This study aimed to investigate the nanobacteria (NB) induced damage to human tubular epithelial HK-2 cells and the potential role of NB in the kidney stone formation.

METHODS:

Serum sample from 15 patients with kidney stone was collected. Four groups were included: control, NB group, nanograde hydroxyapatite (nHAP) and calcium oxalate monohydrate (COM) group. Catalase (CAT), malonaldehyde (MDA) and Na(+)/K(+) ATPase activity was detected in the supernatant at 12 and 24 h. At 12 and 24 h, COM was added.

RESULTS:

At 12 h and 24 h, the CAT in NB group was significantly higher than in control group and nHAP group (P<0.01). CAT at 24 h was significantly higher than in COM group (P<0.01). At 12 h and 24 h, the MDA in NB group was significantly higher than in control group and nHAP group (P<0.01) and significantly lower than in COM group (P<0.01). At 12 h, the Na(+)/K(+) ATPase activity in NB group and nHAP group was significantly lower than in control group, but dramatically increased as compared to COM group (P<0.01). At 24 h, the Na(+)/K(+) ATPase activity in NB group and nHAP group was significantly lower than in control group (P<0.01).

CONCLUSION:

NB may induce lipid peroxidation in HK-2 cells and cause adhesion of HK-2 cells to COM in a time-dependent manner, resulting in damage to HK-2 cells. This injury-causing capability of NB is more potent than nHAP and might be involved in the pathogenesis of kidney stone formation.

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